VAR2CSA-Mediated Host Defense Evasion of Plasmodium falciparum Infected Erythrocytes in Placental Malaria

Over 30 million women living in P. falciparum endemic areas are at risk of developing malaria during pregnancy every year. Placental malaria is characterized by massive accumulation of infected erythrocytes in the intervillous space of the placenta, accompanied by infiltration of immune cells, particularly monocytes. The consequent local inflammation and the obstruction of the maternofetal exchanges can lead to severe clinical outcomes for both mother and child. Even if protection against the disease can gradually be acquired following successive pregnancies, the malaria parasite has developed a large panel of evasion mechanisms to escape from host defense mechanisms and manipulate the immune system to its advantage. Infected erythrocytes isolated from placentas of women suffering from placental malaria present a unique phenotype and express the pregnancy-specific variant VAR2CSA of the Plasmodium falciparum Erythrocyte Membrane Protein (PfEMP1) family at their surface. The polymorphic VAR2CSA protein is able to mediate the interaction of infected erythrocytes with a variety of host cells including placental syncytiotrophoblasts and leukocytes but also with components of the immune system such as non-specific IgM. This review summarizes the described VAR2CSA-mediated host defense evasion mechanisms employed by the parasite during placental malaria to ensure its survival and persistence.

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Transcribed var Genes Associated with Placental Malaria in MalawianWomen

Infection and Immunity ◽

10.1128/iai.01978-05 ◽

2006 ◽

Vol 74 (8) ◽

pp. 4875-4883 ◽

Cited By ~ 65

Author(s):

Michael F. Duffy ◽

Aphrodite Caragounis ◽

Rintis Noviyanti ◽

Helen M. Kyriacou ◽

Ee Ken Choong ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Pregnant Women ◽

Reverse Transcription ◽

Malaria Vaccine ◽

Placental Malaria ◽

Var Genes ◽

Quantitative Reverse Transcription Pcr ◽

Reverse Transcription Pcr ◽

Malaria During Pregnancy

ABSTRACT Determining the diversity of PfEMP1 sequences expressed by Plasmodium falciparum-infected erythrocytes isolated from placentas is important for attempts to develop a pregnancy-specific malaria vaccine. The DBLγ and var2csa DBL3x domains of PfEMP1 molecules are believed to mediate placental sequestration of infected erythrocytes, so the sequences encoding these domains were amplified from the cDNAs of placental parasites by using degenerate oligonucleotides. The levels of specific var cDNAs were then determined by quantitative reverse transcription-PCR. Homologues of var2csa DBL3x were the predominant sequences amplified from the cDNAs of most placental but not most children's parasites. There was 56% identity between all placental var2csa sequences. Many different DBLγ domains were amplified from the cDNAs of placental and children's isolates. var2csa transcripts were the most abundant var transcripts of those tested in 11 of 12 placental isolates and 1 of 6 children's isolates. Gravidity did not affect the levels of var2csa transcripts. We concluded that placental malaria is frequently associated with transcription of var2csa but that other var genes are also expressed, and parasites expressing high levels of var2csa are not restricted to pregnant women. The diversity of var2csa sequences may be important for understanding immunity and for the development of vaccines for malaria during pregnancy.

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Beyond arbitrium: identification of a second communication system in Bacillus phage phi3T that may regulate host defense mechanisms

The ISME Journal ◽

10.1038/s41396-020-00795-9 ◽

2020 ◽

Cited By ~ 2

Author(s):

Charles Bernard ◽

Yanyan Li ◽

Philippe Lopez ◽

Eric Bapteste

Keyword(s):

Public Goods ◽

Host Defense ◽

Communication Systems ◽

Defense Mechanisms ◽

Evolutionary Stability ◽

Lytic Cycle ◽

Host Cells ◽

The Public ◽

Fitness Advantage ◽

Bacillus Phage

Abstract The evolutionary stability of temperate bacteriophages at low abundance of susceptible bacterial hosts lies in the trade-off between the maximization of phage replication, performed by the host-destructive lytic cycle, and the protection of the phage-host collective, enacted by lysogeny. Upon Bacillus infection, Bacillus phages phi3T rely on the “arbitrium” quorum sensing (QS) system to communicate on their population density in order to orchestrate the lysis-to-lysogeny transition. At high phage densities, where there may be limited host cells to infect, lysogeny is induced to preserve chances of phage survival. Here, we report the presence of an additional, host-derived QS system in the phi3T genome, making it the first known virus with two communication systems. Specifically, this additional system, coined “Rapφ-Phrφ”, is predicted to downregulate host defense mechanisms during the viral infection, but only upon stress or high abundance of Bacillus cells and at low density of population of the phi3T phages. Post-lysogenization, Rapφ-Phrφ is also predicted to provide the lysogenized bacteria with an immediate fitness advantage: delaying the costly production of public goods while nonetheless benefiting from the public goods produced by other non-lysogenized Bacillus bacteria. The discovered “Rapφ-Phrφ” QS system hence provides novel mechanistic insights into how phage communication systems could contribute to the phage-host evolutionary stability.

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Gravidity-Dependent Production of Antibodies That Inhibit Binding of Plasmodium falciparum-Infected Erythrocytes to Placental Chondroitin Sulfate Proteoglycan during Pregnancy

Infection and Immunity ◽

10.1128/iai.69.12.7487-7492.2001 ◽

2001 ◽

Vol 69 (12) ◽

pp. 7487-7492 ◽

Cited By ~ 92

Author(s):

Iona O'Neil-Dunne ◽

Rajeshwara N. Achur ◽

Sean T. Agbor-Enoh ◽

Manojkumar Valiyaveettil ◽

Ramachandra S. Naik ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Pregnant Women ◽

Placental Malaria ◽

Chondroitin Sulfate Proteoglycan ◽

Placental Infection ◽

Malaria During Pregnancy ◽

Low Levels ◽

The Difference ◽

Antibody Levels ◽

Kinetics Of

ABSTRACT During pregnancy, Plasmodium falciparum-infected erythrocytes sequester in the placenta by adhering to chondroitin 4-sulfate, creating a risk factor for both the mother and the fetus. The primigravidae are at higher risk for placental malaria than the multigravidae. This difference in susceptibility has been attributed to the lack of antibodies that block the adhesion of infected erythrocytes to placental chondroitin 4-sulfate in primigravid women. However, recent results show that many primigravidae at term have antibody levels similar to those of multigravidae, and thus the significance of antiadhesion antibodies in providing protection against malaria during pregnancy remains unclear. In this study, we analyzed plasma samples from women of various gravidities at different gestational stages for antiadhesion antibodies. The majority of women, regardless of gravidity, had similar levels of antibodies at term. Most primigravidae had low levels of or no antiadhesion antibodies prior to ∼20 weeks of pregnancy and then produced antibodies. Multigravidae also lacked antibodies until ∼12 weeks of pregnancy, but thereafter they efficiently produced antibodies. In pregnant women who had placental infection at term, higher levels of antiadhesion antibodies correlated with lower levels of placental parasitemia. The difference in kinetics of antibody production between primigravidae and multigravidae correlated with the prevalence of malaria in these groups, suggesting that antibodies are produced during pregnancy in response to placental infection. The early onset of efficient antibody response in multigravidae and the delayed production to antibodies in primigravidae appear to account for the gravidity-dependent differential susceptibilities of pregnant women to placental malaria.

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Host-Bacteria Crosstalk at the Dentogingival Junction

International Journal of Dentistry ◽

10.1155/2012/821383 ◽

2012 ◽

Vol 2012 ◽

pp. 1-14 ◽

Cited By ~ 14

Author(s):

M. T. Pöllänen ◽

M. A. Laine ◽

R. Ihalin ◽

V.-J. Uitto

Keyword(s):

Host Defense ◽

Defense Mechanisms ◽

Bacterial Flora ◽

Oral Bacteria ◽

Host Cells ◽

Tooth Surface ◽

Tissue Destruction ◽

Remarkable Change ◽

Bacterial Plaque

The dentogingival junction is of crucial importance in periodontal host defense both structurally and functionally. Oral bacteria exert a constant challenge to the host cells and tissues at the dentogingival junction. The host response is set up to eliminate the pathogens by the innate and adaptive defense mechanisms. In health, the commensal bacteria and the host defense mechanisms are in a dynamic steady state. During periodontal disease progression, the dental bacterial plaque, junctional epithelium (JE), inflammatory cells, connective tissue, and bone all go through a series of changes. The tissue homeostasis is turned into tissue destruction and progression of periodontitis. The classical study of Slots showed that in the bacterial plaque, the most remarkable change is the shift from gram-positive aerobic and facultatively anaerobic flora to a predominantly gram-negative and anaerobic flora. This has been later confirmed by several other studies. Furthermore, not only the shift of the bacterial flora to a more pathogenic one, but also bacterial growth as a biofilm on the tooth surface, allows the bacteria to communicate with each other and exert their virulence aimed at favoring their growth. This paper focuses on host-bacteria crosstalk at the dentogingival junction and the models studying itin vitro.

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Host-defense mechanisms in hidradenitis suppurativa

Archives of Dermatology ◽

10.1001/archderm.113.4.450 ◽

1977 ◽

Vol 113 (4) ◽

pp. 450-453 ◽

Cited By ~ 14

Author(s):

V. C. Dvorak

Keyword(s):

Host Defense ◽

Defense Mechanisms ◽

Hidradenitis Suppurativa

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Effects of Anesthesia, Surgery and Inflammation Upon Host Defense Mechanisms

International Archives of Allergy and Immunology ◽

10.1159/000231358 ◽

1975 ◽

Vol 48 (5) ◽

pp. 706-720 ◽

Cited By ~ 27

Author(s):

M. Schutte ◽

R. DiCamelli ◽

P. Murphy ◽

M. Sadove ◽

H. Gewurz

Keyword(s):

Host Defense ◽

Defense Mechanisms

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The History and Mystery of Alveolar Epithelial Type II Cells: Focus on Their Physiologic and Pathologic Role in Lung

International Journal of Molecular Sciences ◽

10.3390/ijms22052566 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2566 ◽

Cited By ~ 1

Author(s):

Barbara Ruaro ◽

Francesco Salton ◽

Luca Braga ◽

Barbara Wade ◽

Paola Confalonieri ◽

...

Keyword(s):

Host Defense ◽

Defense Mechanisms ◽

Work Of Breathing ◽

Surfactant Proteins ◽

Alveolar Type ◽

Type I ◽

Type Ii ◽

Lung Protection ◽

Alveolar Epithelial ◽

Distal Lung

Alveolar type II (ATII) cells are a key structure of the distal lung epithelium, where they exert their innate immune response and serve as progenitors of alveolar type I (ATI) cells, contributing to alveolar epithelial repair and regeneration. In the healthy lung, ATII cells coordinate the host defense mechanisms, not only generating a restrictive alveolar epithelial barrier, but also orchestrating host defense mechanisms and secreting surfactant proteins, which are important in lung protection against pathogen exposure. Moreover, surfactant proteins help to maintain homeostasis in the distal lung and reduce surface tension at the pulmonary air–liquid interface, thereby preventing atelectasis and reducing the work of breathing. ATII cells may also contribute to the fibroproliferative reaction by secreting growth factors and proinflammatory molecules after damage. Indeed, various acute and chronic diseases are associated with intensive inflammation. These include oedema, acute respiratory distress syndrome, fibrosis and numerous interstitial lung diseases, and are characterized by hyperplastic ATII cells which are considered an essential part of the epithelialization process and, consequently, wound healing. The aim of this review is that of revising the physiologic and pathologic role ATII cells play in pulmonary diseases, as, despite what has been learnt in the last few decades of research, the origin, phenotypic regulation and crosstalk of these cells still remain, in part, a mystery.

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Intercellular Transmission of Naked Viruses through Extracellular Vesicles: Focus on Polyomaviruses

Viruses ◽

10.3390/v12101086 ◽

2020 ◽

Vol 12 (10) ◽

pp. 1086

Author(s):

Francois Helle ◽

Lynda Handala ◽

Marine Bentz ◽

Gilles Duverlie ◽

Etienne Brochot

Keyword(s):

Immune System ◽

Extracellular Vesicles ◽

Rna Viruses ◽

Viral Transmission ◽

Viral Fitness ◽

Host Cells ◽

Dna Viruses ◽

Recent Advances ◽

Viral Particles ◽

Similar Strategy

Extracellular vesicles have recently emerged as a novel mode of viral transmission exploited by naked viruses to exit host cells through a nonlytic pathway. Extracellular vesicles can allow multiple viral particles to collectively traffic in and out of cells, thus enhancing the viral fitness and diversifying the transmission routes while evading the immune system. This has been shown for several RNA viruses that belong to the Picornaviridae, Hepeviridae, Reoviridae, and Caliciviridae families; however, recent studies also demonstrated that the BK and JC viruses, two DNA viruses that belong to the Polyomaviridae family, use a similar strategy. In this review, we provide an update on recent advances in understanding the mechanisms used by naked viruses to hijack extracellular vesicles, and we discuss the implications for the biology of polyomaviruses.

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